There has already been generally known that asymmetric synthetic reactions can be carried out by using a metal complex prepared from an alkoxide or halide of metal such as titanium, aluminum or the like and an optically active compound as a catalyst. Of these, the reaction for synthesizing optically active cyanohydrins according to the asymmetric cyanation of aldehyde is particularly important as an enantioselective reaction increasing the number of carbon atoms, and various cases thereof as shown below have been reported.
(1) a method using a titanium complex with a chiral Schiff base prepared from optically active β-aminoalcohols and salicylaldehyde as a catalyst (Patent Document 1),
(2) a method using a titanium complex or a vanadium complex prepared from an optically active, tetradentate ligand called a salen type as a catalyst (Non-patent Document 1 and Patent Document 2), and
(3) a method using an aluminum complex prepared from an optically active binaphthyl compound as a catalyst (Patent Document 3).
However, the method (1) requires very low reaction temperature, around −78 degree C., and 10 to 20 mol % of the catalyst to obtain corresponding cyanohydrins with high enantioselectivities. In addition, the catalyst gives good enantioselectivities for very limited aldehydes. Regarding the method (2), enantioselectivity of the catalyst is not sufficient for aliphatic aldehydes in particular although the above mentioned problems are improved. The catalyst in the method (3) shows very high enantioselectivity for asymmetric cyanation of various aliphatic and aromatic aldehydes therefore the catalyst is regarded as a versatile catalyst. However, the catalyst is hardly adequate from the practical point of view because cyanating agent must be added for a long period of time, long reaction time, 36 to 70 hours, is required to complete the reaction and low reaction temperature, −40 degree C., is necessary. Reducing the amount of catalyst also remains as a problem to be solved.
On the other hand, in the asymmetric cyanation reaction of ketone, asymmetric catalysts exhibiting high enantioselectivity have hardly been known. One of a few examples include a method using a titanium complex or a rare earth metal complex prepared from an optically active, tridentate ligand derived from glucose as a catalyst, so there has been reported that cyanohydrins with a high optical purity are obtained from various substrates (Patent Document 4).
However, there have not been known asymmetric cyanation catalysts which can be applied to a wide range of substrates, achieve high yield and high enantioselectivity, obtain a desired product within a short period of time, and does not require facilities for the reaction at a low temperature.
Furthermore, there has also been demanded development of asymmetric cyanation catalysts combining industrially desired conditions such that they can be produced with ease and have high activity, and the amount thereof is suppressed low.
Patent Document 1: Japanese Patent Laid-open No. 1993-112518
Patent Document 2: WO02/10095
Patent Document 3: Japanese Patent Laid-open No. 2000-191677
Patent Document 4: Japanese Patent Laid-open No. 2002-255985
Non-patent Document 1: J. Am. Chem. Soc., Vol. 121, p. 3968 (1999)